The ultimate goal of this program is to obtain data which can be used to evaluate the present or potential role of inhibitors of environmental chemical carcinogens. Persuant to this goal are several major objectives. The first is to determine the mechanism of inhibition of chemical carcinogenesis by antioxidants and other compounds found to exert an inhibitory effect. The second is to determine conditions under which inhibition occurs including parameters which will predict the host's capacity to utilize specific inhibitory mechanisms. The third is to determine chemical characteristics which control the ability of compounds to inhibit chemical carcinogenesis. The first part of this renewal is a continuation of efforts at determining the mechanism of inhibition of polycyclic hydrocarbon carcinogenesis by antioxidants. The mechanism by which butylated hydroxyanisole (BHA) causes decreased binding of benzo(a)pyrene (BP) metabolites to DNA in a microsomal system (previously observed) will be studied. BP metabolite patterns produced by incubation of BP with microsomes from normal and BHA fed mice will be determined as will be the activities of enzyme reactions potentially affecting these metabolite patterns. Efforts will be made to elucidate the mechanism by which BHA causes microsomes to have altered cytochrome P-450. Studies to determine the genetic characteristics of responsiveness of microsomes to alteration by BHA will be carried out. Studies of an alternative mechanism by which BHA might inhibit BP carcinogenesis will be continued. This consists of efforts at demonstrating a direct interaction of BHA with BP metabolites. The second part of the proposal will be aimed at inhibiting carcinogenesis due to malonaldehyde and glycialdehyde.